PB1931: LOW SERUM CHOLESTEROL LEVEL AS A SIGNIFICANT PROGNOSTIC FACTOR IMPROVES CLL-IPI IN CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: Rui Gao, Kai-Xin Du, Jinhua Liang, Yi Xia, Jia-Zhu Wu, Yue LI, Bi-Hui Pan, LI Wang, Jianyong LI, Wei Xu
Journal: HemaSphere (2023)

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Hypocholesterolemia possibly due to increased cellular demand and uptake of cholesterol esters is correlated with elevated cancer risk and mortality. Despite remarkable efforts to develop new prognostic models in chronic lymphocytic leukemia (CLL) by incorporating clinical, biological and genetic aberrations, it is quite surprising to find hardly any current CLL prognostic factor or model is established on reprogramed lipid metabolism. Considering the high turnover rate of CLL cells, altered cholesterol level as an easily obtained parameter reflecting overall nutritional status should have its potential in predicting CLL survival. Aims: Our study aims to investigate the correlation between serum lipid profile and CLL clinical characteristics, evaluate the prognostic value of cholesterol levels in CLL and develop a prognostic nomogram incorporating lipid metabolism to facilitate risk stratification. Methods: In our study, 761 eligible newly-diagnosed CLL patients between January 2007 and January 2021 were enrolled and divided into derivation (n=507) and internal validation (n=254) cohorts (2:1). Patients were followed-up until December 2021 with a median follow-up time of 77.5 months. Prognostic nomogram was constructed based on variables associated with cancer-specific survival (CSS) in multivariate Cox regression analyses. Predictive performance of models was evaluated using C-index, area under the curve (AUC), calibration and decision curve analyses. Results: We identified that decreased levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) at diagnosis were significantly associated with worse time-to-first-treatment (TTFT) and CSS (Figure 1A, B, C, D). Patient with concurrently low HDL-C together with low LDL-C had remarkably worse TTFT and CSS compared with those having only low HDL-C, only low LDL-C, or normal HDL-C and LDL-C. Multivariate Cox regression analyses showed that synchronously low HDL-C and LDL-C was an independent prognostic indicator for both TTFT (HR=1.488; 95% CI: 1.187−1.865; P=0.001) and CSS (HR=2.907; 95% CI: 1.848−4.572; P<0.001). CLL patients who achieved complete remission or partial remission had significant increases in post-chemotherapeutic TC, HDL-C and LDL-C levels as compared with baseline, and these elevations were correlated with favorable survival. Furthermore, we developed a nomogram (ModelLipo-IPI) for CSS that integrates all the significant independent factors in the multivariate Cox regression analyses of derivation cohort, including age, stage, β2-MG level, TP53 and IGHV status, and lipid profile (Figure 2E). To investigate the incremental prognostic value of low cholesterol level, a reduced model was also constructed (ModelCLL-IPI) which only consists of five parameters in CLL-international prognostic index (CLL-IPI). The prognostic nomogram ModelLipo-IPI augmenting CLL-IPI with low cholesterol levels yielded better predictive accuracy and discrimination capacity for 3-year and 5-year CSS with highest C-index, largest AUCs and most desirable clinical net benefit both in derivation and internal validation cohorts as compared with ModelCLL-IPI or CLL-IPI alone (Figure 2F, G). Conclusion: Cholesterol profile as a cheap and readily accessible tool has great potential for predicting prognosis in clinical practice of CLL. The application of ModelLipo-IPI may materially improve risk stratification and optimize management of CLL patients.Keywords: Prognostic factor, Cholesterol, Chronic lymphocytic leukemia, International prognostic index